The Vroman Effect is exhibited by protein adsorption to a surface by blood serum proteins. The highest mobility proteins generally arrive first and are later replaced by less motile proteins that have a higher affinity for the surface. A typical example of this occurs when fibrinogen displaces earlier adsorbed proteins on a biopolymer surface and is later replaced by high molecular weight kininogen. In surgical applications and wound healing, a generalized Vroman effect can be applied to all cellular/prosthetic interactions, wherein a foreign body is identified by the denaturation of proteins that attach to the implant surface, and thus label the implant as a foreign body and signal cells to wall off or removed by phagocytosis an implant. Similarly, cells traveling through the extracellular matrix of tissue proceed by laying down proteins from which they derive locomotion. Thus, an implant that prevents protein attachment prevents both labeling of an implant as a foreign body and colonization of the implant by fibrogenic cells and microbes.
Thus, controlling protein adsorption on implantable medical devices is important in controlling the foreign body response, the adverse form of which is chronic inflammation. Chronic inflammation leads to fibrotic encapsulation and the release of several factors that result in apoptosis and abundance of reactive oxygen species.
Biomaterials typically exhibit diverse protein adsorption, leading to mixed layers of partially denatured proteins. These surfaces contain different cell binding sites due to adsorption of proteins such as fibrinogen, immunoglobulin which results in attachment of inflammatory cells such as macrophages and neutrophils. When activated, these cells secret a wide variety of pro-inflammatory and proliferative factors. Hydrophilic surfaces control these events, and absorb little or no protein, primarily due to their dipole interactions with water. Unfortunately, hydrophilic substances generally possess poor volume stability and are susceptible to hydrolytic and enzymatic degradation.
Implants can generally be divided into two categories, those that are absorbable, and those that are intended to be biostable. For those implants that are bioabsorbable, it is important that the absorption rate is sufficiently slow to minimize inflammatory response and local changes in pH. Complete healing of a surgically altered site is widely believed to be about 6 months, if the patient has a normal healing response, for example adequate collagen production and blood supply. In cases where healing is compromised, a bioabsorbable implant may need to provide mechanical integrity for multiple years, while avoiding a foreign body response.
Accordingly, there is a need for a composition useful for medical devices that prevents protein adsorption while possessing volumetric stability and durability in vivo for a desired period of time. Such compositions would be expected to mitigate the foreign body response in vivo.